Background Blood-brain barrier (BBB) breakdown is an early event in the pathogenesis of multiple sclerosis (MS). In a previous study we have found a direct stabilization of barrier characteristics after treatment of bovine brain capillary endothelial cells (BCECs) with human recombinant interferon-beta-1a (IFN-beta-1 alpha) in an in vitro BBB model. In the present study we examined the effect of human recombinant IFN-beta-1 alpha on the barrier properties of BCECs derived from four different species including humans to predict treatment efficacy of IFN-beta-1 alpha in MS patients. Methods We used primary bovine and porcine BCECs, as well as human and murine BCEC cell lines. We investigated the influence of human recombinant IFN-beta-1 alpha on the paracellular permeability for 3H-inulin and 14C-sucrose across monolayers of bovine, human, and murine BCECs. In addition, the transendothelial electrical resistance (TEER) was determined in in vitro systems applying porcine and murine BCECS. Results We found a stabilizing effect on the barrier characteristics of BCECs after pretreatment with IFN-beta-1 alpha in all applied in vitro models: addition of IFN-beta-1 alpha resulted in a significant decrease of the paracellular permeability across monolayers of human, bovine, and murine BCECs. Furthermore, the TEER was significantly increased after pretreatment of porcine and murine BCECs with IFN-beta-1 alpha. Conclusion Our data suggest that BBB stabilization by IFN-beta-1 alpha may contribute to its beneficial effects in the treatment of MS. A human in vitro BBB model might be useful as bioassay for testing the treatment efficacy of drugs in MS.
Useful keywords (using NLM MeSH Indexing)
Blood-Brain Barrier/drug effects*
Capillary Permeability/drug effects
Dose-Response Relationship, Drug
Endothelial Cells/drug effects*
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